A Comparative Study of

Efficacy and Safety of

Ondansetron,
Glycopyrrolate and
Dexamethasone for Post
Operative Nausea
and Vomiting Following
General Aneasthesia
Journal Reading
 Preface
• Post operative nausea and vomiting (PONV) is defined as nausea and/or vomiting occurring within 24 hours after
surgery which significantly contribute to patient’s discomfort, distress and dissatisfaction.
• Nausea, vomiting and retching are among the most common postoperative complaints following general
anesthesia. When severe, PONV is associated with bleeding, electrolyte imbalance, dehydration, pulmonary
aspiration and wound dehiscence resulting in prolonged hospital stay & increased health care cost.
• Ondansetron is a 5-HT3 antagonist, exerts its antiemetic & antinauseant effect by blocking serotonin induced
depolarization of vagal afferent nerves. It was developed to control cancer chemotherapy/ radiotherapy induced
vomiting but later found to be effective in PONV.
• Glycopyrrolate is potent & long acting quaternary antimuscarinic with no central effects. Its antisecretory action
on the bronchial & salivary secretions is an additional feature and hence it is preferred agent in anaesthetic
practice.
• Dexamethasone is a potent and highly selective long acting glucocorticoid. The precise mechanism of its
antiemetic action is not known but may be due to prostaglandins antagonism, serotonin inhibition in the gut and
release of endorphins. It augments the efficacy & reduce the side effects of other antiemetics.
• Hence the present study was taken up to compare the efficacy and safety of three widely used drugs with different
mechanism of action with placebo as prophylactic antiemetic for control of PONV in patients undergoing surgery
under general anesthesia.
methods

Prospective Department of Anestesiology in

Victoria Hospital & Bangalore
Medical College and Research
Institute
Single blind randomized • Place

Placebo-controlled September 2017 to December 2017

• Time
Sample
Age (yr) ASA Grade Type of procedure

18-50 I -II General Anestesia

(elective or emergency
included)

Patiens w/ history of motion sickness

excluded
Patiens w/ history of PONV

80 patiens
Sample preparation
• Pre-anaesthetic evaluation
• Explaining about procedure
• Written informed concent
• Patiens randomly assigned into 4 groups
Independent variable

Group A (n=20) received inj. Ondansetron 4mg i.v

Group B (n=20) received inj. Glycopyrrolate 0.2 mg i.v

Group C (n=20) received inj. Dexamethasone 10 mg i.v

Group D (n=20) received inj. Normal Saline i.v

Fixed treatment
All patiens:
• Induction with inj. Fentanyl 2mcg/kg i.v + Inj. Vecoronium 0.1 mg/kg i.v
• pre Oxygenated 100% for 3 minutes

• Anaesthesia Maintenance with N 2O: O2 = 50 : 50 @ 3lts/min + isoflurane 0.8-1.2%

• Reverse Muscle Relaxan with Neostigmine 0.05 mg/kg + Atropine 15 mcg/kg i.v
Observation
24 hours after surgery they monitored and recorded:
• Hearth rate
• Blood pressure
• Respiratory rate
• Severity nausea and vomiting :

 0 menit • 4 jam
 15 menit • 6 jam
 In Recovery Post Operative
30 menit • 12 jam
 Room Ward
60 menit • 18 jam
 2 jam • 24 jam
• Rescue antiemetic if any episodes of nausea or vomiting occurred Inj.
Metoclopramide 10mg i.v
• Incidence of side effect was recorded in adverse drug reaction form
Statistical analysis
• Performed using Kruskal Wallis test
• Continous variable  mean ± SD (age, weight, duration of
surgery)
• Discrete variable  number of episodes of nausea, vomiting and
number adverse event in each group
• Post hoc analysis using Mann Whitney
• Categorical data (ex:ASA Grade & Gender) compared using chi
square test. With P value <0.05 considered statistically significant
RESULT
 The demographic characteristics

Duration of
Age Sex Weight ASA grade
surgery
Ondansentron group had least number of episodes of nausea and vomiting as compared to
Glycopyrrolate and Dexametasone group
In Normal saline group, the first rescue
antiemetic was requires earlier (within 30
minutes post op) and it is most often used as
compared to that in Ondansentron group in
which the first rescue medication was used very
late after 120 mins post op) and it is less often
used
The most common adverse drug reaction in all
groups is headache.
The other symptoms such as dry mouth and
constipation were seen in Glycopyyrolate group
because of its antisecretoryc property.
DISCUSSION
Post operative nausea and vomiting
(PONV )
- Common distressing complications of anaesthesia.
- Etiology  related to anaesthesia and unrelated to anaesthesia.
 age, gender, weight, history of motion sickness and previous history of PONV.
 Operative factors include type and duration of surgery, surgical skill, post operative pain which
along with anaesthetic management further contributes to increased incidence of PONV
 Intra operative nausea and vomiting hampers surgical procedure, while post operative nausea and
vomiting creates risk of wound dehiscence, besides causing discomfort to patients.
 In the present study, the treatment groups were similar in terms of
patient demographic characteristics, anaesthetic administered and
postoperative rescue medication.

Patients with a history of motion sickness, obese females and previous history
of PONV had been excluded from the study.

The difference in incidence of PONV between the groups might be attributable to the
variation in antiemetic drugs administered.
 In the present study, all the three study medications, ondansetron,
glycopyrrolate, dexamethasone had significant antiemetic effect as
compared to placebo.
Ondansetron had McKenzie and colleagues : Ondansetron is 5-HT3 receptor antagonist, which is effective in
significantly preventing PONV. The effectiveness of intravenous (i.v.) ondansetron as prophylactic
higher antiemetic postoperative antiemetic. ondansetron in a dose of 4mg as well as 8 mg was equally effective in
prophylaxis of PONV
efficacy than
dexamethasone,
but similar to Sadhashivam SK11 et al : efficacy of different doses of ondansetron as a prophylaxis for PONV
glycopyrrolate.
Khalid Ahsan12 et al and Suvalka U13 : anaesthesia were free of emesis with Ondansetron 4-8 mg
given iv for prophylaxis, which was comparable with the results of the present study.

The efficacy of
glycopyrrolate and
dexamethasone was
similar.
Efficacy of ondansentron was better than
glycopyrrolate but was not found to be statistically
significant in preventing PONV.
• Which is akin the previous study, Jain R et al  the effect of
glycopyrrolate on nausea and vomiting during caesarian
section are comparable to ondansentron, with increased
incident of dry mouth

Comparison of glycopyrrolate with

dexamethasone, both showed similar efficacy in
preventing PONV (p value= 0,34)
• Not in consistent with the study: Biswas B N et al  the
efficacy of glycopyrrolate was higher when compared to
dexamethasone
Study by Suvalka U et al showed that efficacy of ondansentron was better than
dexamethasone wih lesser side effects which similar with results of the present study
Between glycopyrrolate and normal salin 
statistically significant
• Conver with the results: Ure D et al and Biswas B N et al 
glycopyrrolate was superior to placebo

Efficacy of dexamethasone was better than

glycopyrrolate but was not found to be statistically
significant in preventing PONV
• Consistent with the study: Khatiwada S et al  the use
dexamethasone prior to subarachnoid block in patients
undergoing total abdominal hysterectomy significantly reduces
the incidence of nausea and vomiting and the requirement of
antiemetic in the postoperative period, with better patient
satisfaction
• Dexamethasone first reported as an antiemetic in patient receiving cancer
chemoteraphy in 1981
• A wide range of doses of dexamethasone (8-32mg) has been used in the management of
PONV and emesis associated with chemoteraphy
• This study  dexamethasone 8mg
The study compared The study included
the antiemetic all types of surgeries
efficacy of 3 drugs under general
with different anaesthesia
mechanism of action
Conclusion
This study concludes that the prophylactic use of ondansetron and glycopyrrolate was
more effective with fewer side effects in reducing the incidence of nausea and vomiting
postoperatively than with dexamethasone.
References
1. Kovac AL. Prevention and treatment of postoperative nausea and vomiting. Drugs; 59: 213–43 (2000).

2. Gan TJ. Post operative nausea and vomiting can it be eliminated? JAMA; 287:1233-1236 (2002).

3. Ramanathan, Augustus, Thiruvengadam, Sundaram M, Deepalakshmi. Efficacy of propofol in preventing postoperative nausea and vomiting:
single blind randomized control study. The Int J of Anaesthesiol.; 7:1092-406 (2003).

4. Dalvi N P, Chimalwar S. A Prospective, Randomised, Double-Blind Comparative Study of IV Granisetron Vs Dexamethasone as Antiemesis
Prophylaxis in Patients Undergoing Elective Abdominal Laparoscopic Surgery. IJSR. NET.; 5(7): 1721-1726 (2016).

5. Sharkey KA, Wallace JL. Treatment of disorders of bowel motility and water flux; antiemetics; agents used in biliary and pancreatic disease.
In: Brunton L, Chabner B, Knollman B. Goodman & Gilman’s the pharmacological basis of therapeutics,12th ed. New York: Mc Graw
Hill;2011.p1227-1228

6. Brown JH, Laiken N. Muscarinic receptor agonist and antagonist. In: Brunton L, Chabner B, Knollman B. Goodman & Gilman’s the
pharmacological basis of therapeutics,12th ed. New York: Mc Graw Hill;2011.p237-238

7. Apfel CC, Kranke P, Katz MH, Goepfert C, Papenfuss T, Rauch S, et al. Volatile anaesthetics may be the main cause of early but not delayed
postoperative vomiting: a randomized controlled trial of factorial design. Br J Anaesth; 88: 659–68 (2002).

8. Gupta P, Jain S. Post operative nausea and vomiting prophylaxis: a comparative study of ondansetron, granisetron and granisetron &
dexamethasone combination after modified radical mastectomy. Saudi J Anaesth; 8(1):67-71 (2014).

9. McKenzie R, Tantisira, Boonrak , Karambelkar, Deepa J, Riley et al: Comparison of ondansetron with ondansetron plus dexamethasone in
the prevention of postoperative nausea and vomiting. Anaesthesia Analgesia; 79: 961-4 (1994).

10. Paventi S, Santevecchi A, Ranieri R. Efficacy of a single-dose ondansetron for preventing post-operative nausea and vomiting after
laparoscopic cholecystectomy with sevoflurane and remifentanil infusion anaesthesia. Eur Rev Med Pharmacol Sci.; 5: 59-63 (2001)
References
11. Sadhasivam Sk, Shende D, Madan R .Prophylactic Ondansetron in Prevention of Postoperative Nausea and
Vomiting following Pediatric Strabismus Surgery. A Dose-Response Study. Anaeathesiol.; 92(4):1035-1042
(2000).

12. Ahsan K, Abbas N, Nadeem Naqvi S M, Murtaza G, Tariq S et al.Comparison of efficacy of Ondansetron
and Dexamethasone combination and Ondansetron alone in preventing postoperative nausea and vomiting after
laparoscopic cholecystectomy. J Pak Med Assoc.; 64(3):242-246 (2014).

13. Suwalka U, Parmar D, Doshi S, Jha P. Efficacy comparison of ondansetron with dexamethasone in
preventing nausea and vomiting in post laparoscopic surgeries. Indian J res rep med sci.; 3(1): 20-22 (2013).

14. Jain R, Sharma S. A comparative study of effects of glycopyrrolate and ondansetron on nausea and vomiting
in cesarean section under spinal anesthesia. Anesth Essay Res.; 9(3): 348-352 (2015)

15. Vrinda Oza ,Srinivasa S, Abhijeet I, Jigisha B, Chhaya A V. Comparison of ondansetron & dexamethasone
in prevention of postoperative

nausea & vomiting in laparoscopic surgery. Int J Biomed Res.; 5(2): 110-112 (2014).

16. Biswas BN, Rudra A, Das SK, Nath S, Biswas SC. A comparative study of glycopyrrolate, dexamethasome
and metoclopramide in control of nausea and vomiting after spinal anesthesia for caesarean delivery. Indian J
Anaesth; 47:198–200 (2003).
References
17. Ure D, James KS, McNeill M, Booth JV. Glycopyrrolate reduces nausea during spinal anaesthesia for
caesarean section without affecting neonatal outcome. Br J Anaesth.; 82:277–9 (1999)

18. Khatiwada S, Bhattarai B, Biswas BK, Pokharel K, Acharya R, Singh SN et.al. Postoperative Nausea and
Vomiting in Patients Undergoing Total Abdominal Hysterectomy Under Subarachnoid Block: a Randomized
Study of Dexamethasone Prophylaxis. Kathmandu Univ Med J.; 38(2):41-45 (2012).

19. Wang J. J.,Ho S. T., Liu H.S., Ho C.M.: Prophylactic antiemetic effect of dexamethasone in women
undergoing ambulatory laparoscopic surgery. British Journal of Anaesthesia; 84(4):459-62 (2000).

20. Gupta P, Jain S. Post operative nausea and vomiting prophylaxis: a comparative study of ondansetron,
granisetron and granisetron & dexamethasone combination after modified radical mastectomy. Saudi J
Anaesth; 8(1): 67-71 (2014).

21. Bano F, Zafar S, Aftab S , Haider S. Dexamethasone Plus Ondansetron for Prevention of Postoperative
Nausea and Vomiting in Patients Undergoing Laparoscopic Cholecystectomy: A Comparison with
Dexamethasone Alone. J Coll Physicians Surg Pak.; 18(5): 265-269 (2008).